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The comparative effectiveness of two dosage forms of metoprolol, the 120mg slow release tablet (SR) administered once daily and the 40mg conventional tablet (CO) given three times daily, on premature ventricular contraction (PVC) and heart rate (HR) was examined in patients with PVC of≥3, 000 beats/24 hr by employing a Holter ECG with a 24-hour monitor using a cross-over design, and changes with time in plasma concentrations after administration of SR and CO were measured.The mean of the PVC values which were monitored three times in the observation period under placebo was 710±184 beats/hr (Mean±S. E.) and the diurnal variation of PVC was high, averaging 34.2±6.5%. In the treatment periods, five patients showed significant reduction of PVC values by more than 25% in comparison to the placebo treated period in one of the intervals, showing reduction values during the whole day, the daytime, and the night-time of 37.8±13.3%, 46.5±15.1%, and-91.7±103.3% under SR, respectively. The reduction rates under CO tended to be higher in comparison to SR, showing 52.6±12.3%, 59.7±11.0% and 24.5±15.0%, respectively. No significant difference was noted between SR and CO . The duration of inhibitory effect on PVC was about 12 hours under SR and about 17 hours under CO.In the treatment periods, HR under both SR and CO was inhibited significantly in comparison with that in the observation period . No significant difference in inhibition of HR was seen between SR and CO. The inhibition on HR under CO was slightly higher than that under SR during the interval from night to early morning . These inhibitions were maintained over 24 hours.The plasma concentrations after administration of SR and CO did not show any significant difference. The plasma concentration level which is considered to be sufficient to inhibit HR was maintained even at 24 hours after administration of SR, (11.3±7.8ng/ml).In conclusion, SR maintained the inhibitory effect on HR for 24 hours similarly to that under CO, but was thought to be inferior to CO in its inhibitory effect on PVC . This may be due to the difference in the threshold plasma concentrations to inhibit HR and PVC and the lower plasma concentrations during night-time in the SR treatment period.

rinshou yakuri/rinshō yakuri

Influence of single adiministration of metoprolol slow release (CF-15 SR) in patients with premature ventricular contractions : Comparison with metoprolol conventional tablet by cross-over study.